The (In)dependence of Alternative Splicing and Gene Duplication
Figure 5
The 3-D Distribution of Physico–Chemical Changes in the Affected Residues of AS and GD
The example of mitogen-activated protein kinase 9 (MAPK9). The example of human MAPK9 illustrates how differences between AS and GD in the distribution of sequence changes result in different distributions of physico–chemical properties across the 3-D structure. The original structure of MAPK9 was homology-modelled after MAPK10 and is shown in blue; the residue changes are indicated following a colour scale related to the associated difference in hydrophobicity (we use the absolute value of the difference in order to avoid too many colours; the colour scale goes from blue to red, where the latter corresponds to the largest change). For comparison purposes, the location of the AS changes in the three structures is indicated by a yellow box. As a hydrophobicity measure, we used the free energy of water to octanol transfer [77].
(A) Alternative splice isoforms of MAPK9.
(B) Gene duplicates of high seq.id. (MAPK10; isoform alpha2, 84% seq.id. to MAPK9).
(C) Gene duplicates of medium seq.id. (MAPK13; 46% seq.id. to MAPK9).
We observe, in accordance with the results from the sequence analysis, that while AS changes are located at a very specific location, GD changes are spread all over the protein surface. As expected, the number of changes between MAPK9 and MAPK13 is the largest. Neither one of MAPK9′s paralogues (MAPK10 and MAPK13) shows a set of residue changes identical to that in the alternative splice variant.